Genomic medicine and the insurance industry. Christoph Nabholz, CRO Assembly, 31 May 2018

Transcription

1 Genomic medicine and the insurance industry Christoph Nabholz, CRO Assembly, 31 May 2018

2 The risk for disease is multi-factorial and depends on genetic and environmental components Genome Genotype Environment Non - Genetic Phenotypes Genotype Thrombosis Schizophrenia Alzheimer Fam. breast cancer Colon cancer syndrome Cystic Fibrosis Huntington s Spectrum of Disease Diabetes Non - Genetic Asthma Lung cancer Car accident Genetic contribution to disease

3 Epigenetics is the adaptive response system of our genome to deal with environmental exposure Genetic Epigenetic Construction Blueprint displays what can be built Foreman decides the order of the construction pieces Biology DNA codes what can be expressed Factors around the DNA decides about the activity of the DNA 3

4 DNA methylation is one of three distinct epigenetic mechanisms Histone Methylgroup Source: celgene.com/epigenetics-potential/ DNA Methylation Histone modification RNA interference Set dynamic expression properties transcription control DNA packaging transcription modulation 4

5 DNA methylation can be used as an indicator to monitor gene activity Hypomethylated Under-methylation Over-methylation XXXXXXXXX Under-methylated: increased gene expression XXXXXXXXX Over-methylated: repressed gene expression Source: 5

6 weight Obesity is a chronic disease with different stages of development and a progressive epigenetic footprint Epigenetic events Genes-Environment interaction Intervention Systemic and signal pathology years Constitution Aggravation Chronic disease Resistance/regain 6

7 Obesity DNA methylation serves as a biomarker for obesity/diabetes disease progression Will the insurance industry start incentivizing healthy behavior and measure outcome by epigenetic monitoring? 7

8 Using DNA methylation as an Aging-Clock (Horvath-Clock) Spreading of DNA methylation on the DNA corresponds to the biological age Horvath, 2013 and Horvath, 2015 (Erratum to Horvath, 2013) Measuring DNA methylation in long-lived individuals revealed that they have a young epigenetic age compared to their chronological age Armstrong et al., 2017 Difference between methylation age and chronological age was associated with increased total, cancer, and CVD-mortality Perna et al., 2016 Source: Horvath,

9 Is there a longevity therapy? Dietary restriction Exercise mtor inhibitors Diabetes drug (Metformin) Hormonal and circulating factors NAD precursors and sirtuin activator Modifiers of senescence and telomere dysfunction Mitochondria targeted therapeutics 9

10 Silicon Valley is building significant capacity Peter Thiel working on mtor gene and the mtor pathways Craig Venter using informatics to compare massive amount of genome data do research on hormones Sergey Brin do research on drugs to improve health and lifespan Larry Ellison do research on drugs to expand lifespan offer biological age tests for Life Insurances 10

11 Aging Altering epigenetic age to extend life expectancy Will the insurance industry start using epigenetic patterns in underwriting? 11

12 Liquid biopsy is a fast and easy blood test which allows for the frequent monitoring of somatic mutations acquired by an evolving cancer 12

13 Age standardised incidence per 100,000 population Learnings from thyroid cancer screening in Korea Over-diagnosis rates from thyroid cancer screening protocols impact Critical Illness claims Long-term guarantees worsened outcome of insurers Exclusions for early cancer diagnosis in new products reduce exposure Gradual increase in thyroid ultrasound screening March 2014 physician coalition to stop screening No mortality improvement from thyroid screening observed Policymaker questioned value of screening guidelines 10 0 Year Thyroid Cancer All Cancers Sources: Korea National Cancer Center, HS Ahn and HG Welch, South Korea s Thyroid-Cancer Epidemic Turning the Tide, NEJM 2015; 373;24 p

14 Cancer Liquid biopsy may become the biomarker platform for molecular guidance of cancer therapy Will the cancer diagnostic definitions change due to new molecular profiles and will Critical Illness claims definitions withstand? 14

15 Fighting genetic disease No alternative treatments available Alternative treatment available Gene therapy Increasing of symptoms Sooner or later lethal Reduces the symptoms Can be eventually cured with time Has the potential to cure the disease and provide a symptom free life 15

16 History of gene manipulation Old (TALEN) versus new (CRISPR) approach TALEN High design effort Inaccurate CRISPR (2012) Easy to apply (cheap) Extremely precise Growing organs in immune tolerant pigs 16

17 Immune cell therapy The big hope for curing cancer Cancer Recognizes cancer cell Cancer T-cell Cancer T-cell No action needed, I am totally harmless Cancer treatment T-cell Recognizes cancer cell Cancer Cancer T-cell Activates immune response 17

18 Insurance impact of CRISPR Casualty Life & Health Biohacking Modified organisms may escape and lead to ecosystem impact Genetically Modified Organism Regulatory restriction may lead to food recall Medical malpractice Fatalities and health consequences may lead to liabilities New promising therapies Small patient groups with very high cost to health care system Risk of developing diseases Good genes turn into bad ones and cause devastating outcomes Enhanced life span Higher life expectancy will have pricing implications to pension, life insurance and disability insurance 18

19 Gene Therapy CRISPR is cheap, precise, effective and the big hope for cancer cure Will the insurance industry provide a solution to gene therapy or is it too risky? 19

20 Outlook on big hopes for Genomic Medicine Altering the epigenetic DNA methylation is the big hope for extending human longevity Will we find a new drug to increase lifespan? Will the insurance industry use epigenetic footprints as a tool to underwrite the real biological age? Can dynamic epigenetic changes be used to track and incentivise healthy living? Liquid biopsy is the big hope for guiding molecular cancer therapy approaches Will new molecular profiles define new cancer diagnosis criteria and guide therapy approaches? How will our Critical Illness definitions withstand the new molecular definitions coming to clinical practice? Will we see cancer over-diagnosis rates increase with this new diagnostic tool? Gene therapy approaches are the big hope for cancer cure Will this new technology be save and ethically justified? How effective will cancer immune cell therapy approaches be? Will the insurance industry be able provide insurance solutions? 20

21 21

22 Legal notice 2018 Swiss Re. All rights reserved. You are not permitted to create any modifications or derivative works of this presentation or to use it for commercial or other public purposes without the prior written permission of Swiss Re. The information and opinions contained in the presentation are provided as at the date of the presentation and are subject to change without notice. Although the information used was taken from reliable sources, Swiss Re does not accept any responsibility for the accuracy or comprehensiveness of the details given. All liability for the accuracy and completeness thereof or for any damage or loss resulting from the use of the information contained in this presentation is expressly excluded. Under no circumstances shall Swiss Re or its Group companies be liable for any financial or consequential loss relating to this presentation. 22